Differential Expression of Connective Tissue Growth Factor in Microglia and Pericytes in the Human Diabetic Retina

Abstract

Abstract: : Purpose. Connective tissue growth factor (CTGF) stimulates fibrosis and angiogenesis and has a role in the pathogenesis of diabetic nephropathy. In cultured retinal vascular cells CTGF is induced by VEGF-A, indicating a possible role of CTGF in diabetic retinopathy (DR). To further characterize this role we investigated CTGF expression in normal and diabetic human retina. Methods. CTGF expression patterns were studied by immunohistochemistry in the retina of eyes of 36 diabetic patients and 18 non-diabetic controls and compared with staining of markers of endothelial cells (CD31), pericytes (NG2), astrocytes (GFAP) and microglia (CD45). Results. In control retinas and in 16 out of the 36 diabetic cases, distinct, specific and predominant staining of CTGF was observed in microglia, situated around or in close vicinity of retinal capillaries. In addition, within the vascular wall, sporadic staining of pericytes was also observed. In contrast, in the retina of 20 out of 36 persons with diabetes, pericytes were the predominant cell type expressing CTGF. Conclusions. Our study shows for the first time that CTGF is expressed in microglia in the retina. In a large subset of diabetic persons, CTCF is predominantly expressed in microvascular pericytes. This may parallel the reported VEGF- and glucose-induced CTGF expression in retinal pericytes and glomerular mesangial cell in vitro, respectively. Our results suggest a distinct, but as yet unidentified, role of CTGF in the pathogenesis of diabetic retinopathy.

Keywords: growth factors/growth factor receptors • diabetic retinopathy • immunohistochemistry